Fibromyalgia (FMS), defined as the presence of both chronic widespread pain and the finding of 11/18 tender points on examination, affects 2% of the general population. The two treatment approaches that have received the most attention in FMS management and research are cognitive behavioral therapy (CBT) and drug therapy. Whereas drug therapy is most effective for improving the symptoms associated with FMS, CBT has been shown to be more useful for improving the FMS-related disability. Given the fact that mono-therapies (drug or CBT alone) appear to only produce modest reductions in pain, it is time to consider more careful study of combination treatment that includes drug and CBT to optimize treatment response. More importantly, little is known about the mechanisms of how two different treatment strategies would work alone or in combination to enhance outcomes. Therefore, we propose to conduct a 3-arm randomized attention-controlled trial whose primary aim is to test the feasibility of combined CBT and duloxetine treatment approach, and obtain preliminary estimates of its effect for use in designing a larger trial. This pilot study will enroll 48 FMS patients, randomizing them to one of the 3 groups: (1) combination CBT-duloxetine, (2) CBT-placebo, or (3) duloxetine-education (attention) group. From week 1 to 9, subjects will receive 8 sessions of telephone-delivered CBT or educational instructions. Additionally, from week 1 to 21, subjects will receive duloxetine or placebo. Outcome assessments at baseline (week 1), week 9 and week 21 will include the following: self-report pain severity and physical function, pain-related beliefs and coping and evoked pain sensitivity. This program of research would enable us to explore biological mechanisms of a psychological-based therapy, and the psychological mechanisms of a biological-based therapy. PUBLIC HEALTH RELEVANCE: Given the fact that mono-therapies (drug or CBT alone) appear to only produce modest reductions in pain, the proposed research is significant because the combination CBT and duloxetine has considerable potential to maximize treatment response. More importantly, exploring the biological and psychological mechanisms underlying combination treatment may pave the way for developing new treatments for FMS sufferers.